Amantadine
Amantadine
Generic Name
Amantadine
Mechanism
Amantadine acts through two primary mechanisms:
| Mechanism | Clinical Relevance |
| Inhibition of viral RNA uncoating | Blocks the M2 proton channel of influenza A virions, preventing acidification of the viral envelope and subsequent release of viral RNA into the host cell. |
| NMDA receptor antagonism & dopaminergic augmentation | Blocks glutamate‑mediated NMDA receptors, reduces dopamine turnover, and enhances striatal dopamine release – beneficial in Parkinson disease and levodopa‑induced dyskinesia. |
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Pharmacokinetics
- Absorption: Oral bioavailability ~60 %. Peak plasma concentration 0.5–2 h post‑dose.
- Distribution: Moderate volume of distribution (≈ 0.8 L/kg). Moderately crosses the blood–brain barrier.
- Metabolism: Minimal hepatic metabolism; mostly excreted unchanged.
- Elimination: Renal excretion 70–80 % unchanged; terminal half‑life ~10–12 h in normal renal function, extended to 20–25 h with creatinine clearance <30 mL/min.
- Drug Interactions: Concomitant use with drugs affecting renal function (e.g., ACE inhibitors, diuretics) or drugs that lower seizure threshold (carbamazepine, valproate) may necessitate dose adjustment.
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Indications
- Influenza A – Treatment or prophylaxis (200 mg PO on day 1, 100 mg PO daily thereafter).
- Parkinson Disease – Low‑dose adjunctive therapy (≤ 200 mg PO daily) or early initiation in mild‑to‑moderate disease.
- Levodopa‑Induced Dyskinesia – 100 mg PO three times daily until dyskinesia abates.
- Other – Off‑label uses include restless legs syndrome, dysphonia, tremor, and migraine prophylaxis (clinical evidence is limited).
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Contraindications
- Contraindications
- Severe renal impairment (CrCl < 15 mL/min) – avoid or use extreme caution.
- Known hypersensitivity to amantadine or its excipients.
- Warnings
- Neuropsychiatric: Psychosis, delirium, agitation; avoid in patients with active psychiatric disorders.
- Seizures: Low threshold; monitor in epileptics.
- Ocular toxicity: Rare, but monitor vision changes, especially in high‑dose or prolonged therapy.
- Pregnancy: Category C – use only if benefits outweigh risks.
- Renal Considerations: Renal dose adjustment necessary; monitor serum creatinine and electrolytes.
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Dosing
| Condition | Starting Dose | Titration | Max Dose | Route | Notes |
| Parkinson Disease | 100 mg PO daily | Incrementally ↑ by 100 mg weekly to 200 mg daily | 200 mg daily | Oral | Often start after 3–4 months of levodopa or earlier in slow responders. |
| Levodopa‑Induced Dyskinesia | 100 mg PO TID | Up to 200 mg TID if needed | 200 mg TID | Oral | Discontinue when dyskinesias resolve. |
| Influenza A (Adults) | 200 mg PO day 1 | 100 mg PO daily thereafter | 100 mg PO daily | Oral | Prophylaxis in unsheltered individuals or immunocompromised. |
| Renal impairment (CrCl 30–60 mL/min) | 50 mg PO daily | titrate as tolerated | 100 mg daily | Oral | Monitor CrCl every 2–3 weeks initially. |
• Administration Tip: Take with food to reduce gastrointestinal irritation; avoid exceeding 200 mg/day unless under strict supervision.
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Adverse Effects
- Common (≥ 5 %)
- *Dysphoria, insomnia, vivid dreams*
- *Headache, dizziness, nausea*
- *Extrapyramidal symptoms* – dystonia, dyskinesia
- *Psychomotor agitation*
- Serious (≤ 1 %)
- *Seizures* – especially in patients with pre‑existing epilepsy or on other seizure‑lowering drugs.
- *Neuropsychiatric* – hallucinations, delusions, depression.
- *Acute kidney injury* – due to volume depletion or contrast reactions.
- *Retinal pigmentary changes* – rare; monitor vision in long‑term use.
- *Increased intracranial pressure* – particularly in cystic lesions.
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Monitoring
| Parameter | Frequency | Rationale |
| Renal function (CrCl/BUN) | Baseline; every 2–4 weeks in renal disease | Dose adjustment required |
| Serum electrolytes | At baseline; first dose; then monthly | Risk of hyperkalemia, hyponatremia |
| Neurologic assessment | Baseline; 1 week after dose escalation | Detect early dyskinesia or neuropsychiatric changes |
| Blood pressure & heart rate | Baseline; every 2–3 months | Mild tachycardia possible |
| Ophthalmologic exam | Screening in patients >6 months therapy | Detect visual changes early |
| Pregnancy test (women of childbearing age) | Prior to initiation | Category C drug |
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Clinical Pearls
- Kidney‑Centric Dosing: Because 80 % of amantadine is renally excreted unchanged, patients with reduced CrCl need dramatic dose reductions; a 30 % reduction often suffices for CrCl 30–60 mL/min, while CrCl < 15 mL/min warrants suspension.
- Seizure Considerations: If you must treat an epileptic patient, co‑administer levetiracetam rather than phenobarbital to avoid added Na‑channel blocking effects.
- Parkinson Off‑Label Use: In early PD, initiate after 4–6 months of levodopa if pill‑on/off fluctuations begin; benefits are rapid but transient.
- Influenza ‘Catch‑Up’: For patients who started on an antiviral but miss the 2 h window, a full dose of amantadine can still afford some benefit, albeit reduced.
- Psychiatric Home‑Check: Re‑evaluate patients after 4 weeks of therapy for depression or suicidal ideation – especially in older adults with pre‑existing mood disorders.
- Drug Interaction Lighter Ticket: Unlike ribavirin, amantadine does not heavily interact with CYP enzymes, but it can displace other renally cleared agents, so monitor serum levels of e.g., lithium.
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• *Prepared to serve as a quick‑reference, evidence‑based snapshot of Amantadine for clinical practice and exam review.*